The aim of this research is to discover new chemical entities that are efficacious as anti-addictive agents. We will synthesize target compounds that are structurally related to known Iboga alkaloids. This will involve chemical synthesis of novel compounds and general functional group manipulation. In Phase 1 of this proposal 5-8 analogs of the synthetic Iboga alkaloid 18-MC will be synthesized in parallel for subsequent testing in both in vitro and in vivo models of drug seeking behavior. Success in Phase 1 will set the stage for a more intensive chemistry and biology discovery program in Phase 2. PROPOSED COMMERCIAL APPLICATION: The ultimate goal of this research is to commercialize a new chemical entity which treats the addictive effects of one or more drugs of abuse, such as cocaine, amphetamine, alcohol or nicotine.